Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, King's Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
Nucleic Acids Res. 2012 Apr;40(7):2869-83. doi: 10.1093/nar/gkr1106. Epub 2011 Dec 2.
Post-transcriptional gene regulation is essential to eukaryotic development. This is particularly emphasized in trypanosome parasites where genes are co-transcribed in polycistronic arrays but not necessarily co-regulated. The small CCCH protein, TbZFP3, has been identified as a trans-acting post-transcriptional regulator of Procyclin surface antigen expression in Trypanosoma brucei. To investigate the wider role of TbZFP3 in parasite transmission, a global analysis of associating transcripts was carried out. Examination of a subset of the selected transcripts revealed their increased abundance through mRNA stabilization upon TbZFP3 ectopic overexpression, dependent upon the integrity of the CCCH zinc finger domain. Reporter assays demonstrated that this regulation was mediated through 3'-UTR sequences for two target transcripts. Global developmental expression profiling of the cohort of TbZFP3-selected transcripts revealed their significant enrichment in transmissible stumpy forms of the parasite. This analysis of the specific mRNAs selected by the TbZFP3mRNP provides evidence for a developmental regulon with the potential to co-ordinate genes important in parasite transmission.
转录后基因调控对真核生物的发育至关重要。在锥虫寄生虫中，这种调控尤为重要，因为基因在多顺反子阵列中被共同转录，但不一定被共同调控。小型 CCCH 蛋白 TbZFP3 已被鉴定为一种反式作用的转录后调节因子，可调节布氏锥虫 Procyclin 表面抗原的表达。为了研究 TbZFP3 在寄生虫传播中的更广泛作用，对相关转录本进行了全局分析。对选定的转录本子集的检查表明，它们的丰度通过 TbZFP3 异位过表达而增加，这依赖于 CCCH 锌指结构域的完整性。报告基因分析表明，这种调节是通过两个靶转录本的 3'UTR 序列介导的。对 TbZFP3 选择的转录本进行的全球发育表达谱分析表明，它们在寄生虫可传播的短尾形式中显著富集。对 TbZFP3mRNP 选择的特定 mRNA 的分析为发育调节子提供了证据，该调节子有可能协调在寄生虫传播中重要的基因。
